Header

UZH-Logo

Maintenance Infos

Canakinumab in adults with steroid-refractory pyoderma gangrenosum


Kolios, A G A; Maul, J -T; Meier, B; Kerl, K; Traidl-Hoffmann, C; Hertl, M; Zillikens, D; Röcken, M; Ring, J; Facchiano, A; Mondino, C; Yawalkar, N; Contassot, E; Navarini, A A; French, L E (2015). Canakinumab in adults with steroid-refractory pyoderma gangrenosum. British Journal of Dermatology, 173(5):1216-1223.

Abstract

Background: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids.
Objectives: To determine whether canakinumab is an effective and safe treatment in PG.
Methods: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150–300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least −1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels.
Results: Interleukin (IL)-1β and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other.
Conclusions: Our data indicate that IL-1β plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

Abstract

Background: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids.
Objectives: To determine whether canakinumab is an effective and safe treatment in PG.
Methods: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150–300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least −1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels.
Results: Interleukin (IL)-1β and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other.
Conclusions: Our data indicate that IL-1β plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

Statistics

Citations

1 citation in Web of Science®
8 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

2 downloads since deposited on 09 Dec 2015
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:09 Dec 2015 16:33
Last Modified:05 Apr 2016 19:35
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0007-0963
Publisher DOI:https://doi.org/10.1111/bjd.14037
PubMed ID:26471257

Download

Preview Icon on Download
Content: Published Version
Filetype: PDF - Registered users only
Size: 545kB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations